A common difficulty in managing type 1 diabetes mellitus (T1DM) is hypoglycemia (low blood sugar). This complication is particularly common during childhood. Extreme hypoglycemia can cause coma or death, but less severe hypoglycemia can have consequences for cognitive function. However, it is not well understood how specific these cognitive consequences are and what their neural mechanisms might be, nor how these effects may differ across neural development. We propose to address these important questions. We hypothesize that severe hypoglycemia has a deleterious and specific effect on the hippocampus, a region particularly sensitive to metabolic insults, and on long-term memory, a skill that relies upon the integrity of the hippocampus, in children with T1DM. Using both retrospective and prospective methods, we will determine if the hippocampus is smaller in children with a history of repeated severe hypoglycemia. These measures will be obtained with high resolution structural magnetic resonance imaging and reliable volumetric measurements. We also will determine if reduced hippocampal volumes correlate with reduced long-term memory function. Memory function will be measured in part by a well-validated spatial delayed response measure that we have previously shown to be sensitive to repeated severe hypoglycemia in children with T1DM. We hypothesize that these effects will follow a developmental trajectory, with greater vulnerability in children who experienced hypoglycemia at younger ages due to interruption of critical developmental processes or to increased susceptibility for neuronal impact. The information obtained in this study will be important for the development of optimal treatment regimens for T1DM that minimize cognitive risk and maximize clinical benefit across the lifespan. [unreadable] [unreadable]